It is the purpose of this project to conceive, conduct and communicate the results of original research in the area of genetic manipulation of mammalian cells using the techniques of cell fusion, cellular hybridization and cybridization to produce unique material for the molecular genetic analysis of cellular events. Of prime importance in the laboratory now is the genetic system in mammalian mitochondria. The mapping of recombinations between mitochondrial DNA molecules is being studied using restriction enzymes and cRNA-DNA hybridization. The several distinctive subspecies of mouse are proving to be adequately marked material for such studies. Transformation to chloramphenicol resistance of chloramphenicol sensitive cell strains by mitochondrial DNA from chloramphenicol resistant mutant cell strains is being explored as a means to introduce new genes into mammalian cells so that the impact of such genetic surgery can be evaluated. BIBLIOGRAPHIC REFERENCES: Grollman, E.F., Lee, G., Ambesi-Impiombato, F. S., Meldolesi, M.F., Aloj, S.M., Coon, H.G., Kaback, H.R. and Kohn, L.D.: Effects of thyrotropin on the thyroid cell membrane: Hyperpolarization induced by hormone-receptor interaction. Proc. Nat. Acad. Sci. (in press) 1977. Nissley, P.S., Short, P.A., Rechler, M.M., Podskalny, J.M. and Coon, H.G.: Proliferation of buffalo rat liver cells in serum-free medium does not depend upon multiplication stimulating activity (MSA). Cell (in press) 1977.